The experiments of this proposal would analyze the plastic modifications of central neuronal circuitry which occur in response to brain lesions in adult rats. Both the structural alterations, and the functional consequences of afferent reorganization would be analyzed. Previous studies have shown that unilateral destruction of the entorhinal cortex of the rat induces a proliferative response in the afferents from the contralateral entorhinal cortex, which sprout to reinnervate some of the neurons which had lost their normal input as a consequence of the lesion. This process of post-lesion synaptogenesis is analyzed in this model system, determining 1) What is the nature of the changes which occur in surviving connections following the lesions? 2) What cytological and morphological changes occur in cells which are sprouting? 3) What are the physiological consequences of the changes in circuitry which result from the lesions? 4) Does this sort of reorganization of brain circuitry occur following lesions in a variety of mammals (for example, the cat) or is it unique to less phylogenitically advanced mammals such as the rat?